Process for preparing chiral diphosphines

ABSTRACT

Compounds of formula VII are described:  
                 
 
     wherein A represents phenyl or naphthyl and  
     Ar 1  and Ar 2  independently represent a saturated or aromatic carbocyclic group. The compounds may be prepared by reducing the nitrile functions of a compound of formula I:

[0001] The invention relates to a process for preparing chiraldiphosphines that are useful as bidentate ligands in the synthesis ofcatalysts based on transition metals intended for asymmetric catalysis.

[0002] Asymmetric catalysis has developed considerably in recent years.It has the advantage of leading directly to the preparation of opticallypure isomers by asymmetric induction without it being necessary toresolve racemic mixtures.

[0003] 2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl (BINAP) is an exampleof a diphosphorus ligand commonly used to prepare metal complexes forthe asymmetric catalysis of hydrogenation, carbonylation andhydrosilylation reactions, C—C bond forming reactions (such as allylicsubstitutions or Grignard cross-couplings) or even asymmetricisomerization reactions of allylamines.

[0004] The development of novel chiral ligands is desirable so as toimprove the enantioselectivity of the reactions and, more generally, thegeneral conditions for carrying out these reactions.

[0005] The present invention more specifically provides a process forpreparing diphosphorus bidentate chiral ligands of2,2′-bis(diarylphosphino)-1,1′-binaphthyl and2,2′-bis(diarylphosphino)-1,1′-biphenyl type that are functionalized onthe binaphthyl or biphenyl groups, respectively. These ligands,coordinated to transition metals such as ruthenium or rhodium, formcomplexes that are useful in the asymmetric catalysis of variousreactions and more particularly of asymmetric hydrogenation reactions.

[0006] The ligands prepared according to the process of the inventionare in particular the dicyano derivatives of formula I:

[0007] in which:

[0008] A represents phenyl or naphthyl; and

[0009] Ar₁ and Ar₂ independently represent a saturated aromatic orcarbocyclic radical.

[0010] In the context of the invention, the phenyl and naphthyl radicalsare optionally substituted.

[0011] According to the invention, the term “carbocyclic radical” meansan optionally substituted, preferably C₃-C₅₀ monocyclic or polycyclicradical. Preferably it is a C₃-C₈ radical, which is preferably mono-,bi- or tricyclic.

[0012] The carbocyclic radical may comprise a saturated portion and/oran aromatic portion.

[0013] When the carbocyclic radical comprises more than one cyclicnucleus (in the case of polycyclic carbocycles), the cyclic nuclei maybe fused in pairs or attached in pairs via σ bonds.

[0014] Examples of saturated carbocyclic radicals are cycloalkyl groups.

[0015] Preferably, the cycloalkyl groups are saturated cyclichydrocarbon-based radicals that are preferably C₃-C₁₈ and better stillC₃-C₁₀, and in particular cyclopentyl, cyclohexyl, cycloheptyl,cyclooctyl, adamantyl or norbornyl radicals.

[0016] Examples of aromatic carbocyclic radicals are (C₆-C₁₈)aryl groupsand in particular phenyl, naphthyl, anthryl and phenanthryl.

[0017] The substituents on the phenyl, naphthyl and carbocyclic radicalsare such that they do not interfere with the reactions involved in theprocess of the invention. These substituents are inert under theconditions involved in bromination (step i), esterification (step ii),nucleophilic substitution (step iii) and coupling reactions.

[0018] Preferably, the substituents are alkyl or alkoxy groups.

[0019] The term “alkyl” means a saturated, linear or branchedhydrocarbon-based radical containing in particular up to 25 carbon atomsand, for example, from 1 to 12 carbon atoms and better still from 1 to 6carbon atoms.

[0020] Examples of alkyl groups are methyl, ethyl, propyl, isopropyl,butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, 2-methylbutyl,1-ethylpropyl, hexyl, iso-hexyl, neohexyl, 1-methylpentyl,3-methylpentyl, 1,1-dimethylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl,1-methyl-1-ethylpropyl, heptyl, 1-methylhexyl, 1-propylbutyl,4,4-dimethylpentyl, octyl, 1-methyl-heptyl, 2-ethylhexyl,5,5-dimethylhexyl, nonyl, decyl, 1-methylnonyl, 3,7-dimethyloctyl and7,7-dimethyloctyl radicals.

[0021] In a particularly advantageous manner, the dicyano derivatives offormula I are such that:

[0022] represents naphthyl or phenyl, optionally substituted with one ormore radicals chosen from (C₁-C₆)alkyl and (C₁-C₆) alkoxy; and

[0023] Ar₁ and Ar₂ independently represent a phenyl group optionallysubstituted with one or more (C₁-C₆)alkyl or (C₁-C₆)alkoxy; or a(C₄-C₈)cyclcoalkyl group optionally substituted with one or more(C₁-C₆)alkyl groups.

[0024] Examples of preferred alkyl groups are, in particular, methyl,ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl,neopentyl, 2-methylbutyl, 1-ethylpropyl, hexyl, isohexyl, neohexyl,1-methylpentyl, 3-methylpentyl, 1,1-dimethylbutyl, 1,3-dimethylbutyl,2-ethylbutyl and 1-methyl-1-ethylpropyl.

[0025] Advantageously, the alkyl radical contains from 1 to 4 carbonatoms.

[0026] The term “alkoxy” denotes an —O-alkyl radical in which alkyl isas defined above.

[0027] Advantageously, the cycloalkyl groups are chosen from cyclobutyl,cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl.

[0028] It should be understood that, according to the invention, each ofthe naphthyl and phenyl groups representing A may be substituted.

[0029] Among the ligands of formula I that are preferred are those forwhich Ar₁ and Ar₂ are, independently, phenyl optionally substituted withmethyl or tert-butyl; or (C₅-C₆)cycloalkyl optionally substituted withmethyl or tert-butyl.

[0030] The compounds that are most particularly preferred are those offormula I in which Ar₁ and Ar₂ are identical. A clearly preferredmeaning of Ar₁ and Ar₂ is optionally substituted phenyl.

[0031] Moreover, it is preferred for A to represent naphthyl optionallysubstituted with one to five and preferably one to two groups chosenfrom (C₁-C₆)alkyl and (C₁-C₆)alkoxy. Better still, A representsunsubstituted naphthyl.

[0032] When A represents optionally substituted phenyl, it is preferredfor this phenyl to be substituted in the meta position relative to thegroup PAr₁Ar₂ with (C₁-C₆)alkyl or (C₁-C₆)alkoxy and better still withmethyl or methoxy, the other positions of the phenyl, radical beingunsubstituted.

[0033] One group of compounds that is more particularly preferredconsists of the compounds of formula I with a C₂ axis of symmetry, withthe exclusion of any element of symmetry.

[0034] The notion of the C₂ axis of symmetry is described in “Elementsof Stereochemistry”, Wiley, New York, 1969 and in “Advanced OrganicChemistry”, Jerry March, Stereochemistry, Chapter 4.

[0035] Among this last group of preferred compounds especiallydistinguished are the compounds of formulae Ia and Ib below:

[0036] in which Ar₁ and Ar₂ are as defined above and S represents asubstituent which is compatible with the reactions involved, and inparticular alkyl or alkoxy, which is preferably C₁-C₆,

[0037] in which Ar₁ and Ar₂ are as defined above.

[0038] The process of the invention more specifically comprises thesteps consisting in:

[0039] i) brominating a diol of formula II:

[0040] in which A is as defined above, using a suitable brominatingagent so as to obtain a dibromo compound of formula III:

[0041] in which A is as defined above;

[0042] ii) esterifying the compound of formula III obtained in thepreceding step by the action of a sulfonic acid or an activated formthereof, so as to obtain the corresponding disulfonate;

[0043] iii) substituting the two bromine atoms with cyano groups byreacting the disulfonate obtained in the preceding step with a suitablenucleophilic agent so as to obtain the corresponding nitrile;

[0044] iv) coupling a phosphine of formula VI:

XPAr₁Ar₂   VI

[0045] in which X represents a hydrogen atom or a halogen atom and Ar₁and Ar₂ are as defined above, with the nitrile obtained in the precedingstep, in the presence of a catalyst based on a transition metal, so asto obtain the expected compound of formula I.

[0046] In step (i), the phenyl or naphthyl nucleus, respectively, of thediol of formula II is brominated by the action of a suitable brominatingagent.

[0047] When A is an unsubstituted phenyl nucleus or a nucleus bearing asubstituent in the meta position relative to the OH group, such as(C₁-C₆)alkyl or (C₁-C₆)alkoxy, the corresponding diol of formula IIa:

[0048] in which S₁and S₂ are as defined for S above or independentlyrepresent a hydrogen atom or an alkyl or alkoxy group, which ispreferably C₁-C₆, gives the corresponding bromo compound of formulaIIIa:

[0049] in which S₁ and S₂ are as defined above.

[0050] When A is a naphthyl nucleus, the bromination of thecorresponding diol of formula IIb:

[0051] gives compound IIIb below:

[0052] More generally, the hydroxyl groups present on the phenyl andnaphthyl nuclei orient the electrophilic reaction such that the positionof the bromine atoms on these nuclei is well defined.

[0053] The bromination reaction of phenyl or naphthyl nuclei is anelectrophilic reaction which is readily performed by the action of Br₂on the corresponding diol.

[0054] This reaction may be carried out in the presence of a catalystsuch as a Lewis acid and in particular iron chloride. However, since thehydroxyl groups present on the phenyl and naphthyl nuclei activate thesenuclei, the bromination is readily performed in the absence of anycatalyst.

[0055] The diols of formula II are so reactive that it is desirable tocarry out the bromination at low temperature, for example between −78°and −30° C. and preferably between −78 and −50° C.

[0056] According to one preferred embodiment of the invention, thebromination takes place in an inert aprotic solvent such as ahaloaromatic hydrocarbon (for example chlorobenzene or dichlorobenzene);a nitroaromatic hydrocarbon such as a nitrobenzene; an optionallyhalogenated aliphatic hydrocarbon such as hexane, heptane, methylenechloride, carbon tetrachloride or dichloroethane; or an alicyclichydrocarbon.

[0057] In general, aromatic hydrocarbons with electron-poor aromaticnuclei, i.e. nuclei bearing one or more electron-withdrawingsubstituents, may be used.

[0058] Preferred solvents which may be mentioned are haloaliphatichydrocarbons and in particular methylene chloride.

[0059] As a variant, it is possible to perform the process in glacialacetic acid as solvent. Under these conditions, a solution of bromine inacetic acid is generally added dropwise to a solution of the diol II inacetic acid.

[0060] Whether the process is performed in the presence or absence ofacetic acid, an excess of the brominating agent relative to the diol IIis used.

[0061] Preferably, the molar ratio of the brominating agent to the diolII ranges between 2 and 5 and better still between 2 and 3.

[0062] When the process is performed in solution, the concentration ofthe reagents may vary within a very wide range between 0.01 and 10mol/l, for example between 0.05 and 1 mol/l.

[0063] In step (ii), the hydroxyl functions of the diol III areesterified by the action of a sulfonic acid or an activated formthereof, so as to obtain the corresponding disulfonate.

[0064] According to the invention, the nature of the sulfonic acid usedis not a deciding factor per se.

[0065] Advantageously, the sulfonic acid has the formula:

P—SO₂—OH

[0066] in which P represents a hydrocarbon-based aliphatic group; anaromatic carbocyclic group; or an aliphatic group substituted with anaromatic carbocyclic group.

[0067] The expression “hydrocarbon-based aliphatic group” means inparticular an alkyl group as defined above, which is optionallysubstituted. The nature of the substituent is such that it does notreact under the conditions of the esterification reaction. A preferredexample of a substituent for an alkyl group is a halogen atom such asfluorine, chlorine, bromine or iodine.

[0068] The expression “aromatic carbocyclic group” means mono- orpolycyclic aromatic groups and in particular the mono-, bi- or tricyclicgroups defined above, and for example phenyl, naphthyl, anthryl orphenanthryl.

[0069] The aromatic carbocyclic group is optionally substituted. Thenature of the substituent is not critical provided that it does notreact under the esterification conditions. Advantageously, thesubstituent is optionally halogenated alkyl, alkyl being as definedabove and halogen representing chlorine, fluorine, bromine or iodine,and preferably chlorine. As an example, “optionally halogenated alkyl”denotes perfluoroalkyl such as trifluoromethyl or pentafluoroethyl.

[0070] According to one preferred embodiment of the invention, thesulfonic acid has the formula:

P—SO₂—OH

[0071] in which P represents (C₆-C₁₀)aryl optionally substituted withone or more optionally halogenated (C₁-C₆)alkyl; optionally halogenated(C₆-C₁₀) alkyl; or (C₆-C₁₀)aryl (C₁-C₆)alkyl in which the aryl group isoptionally substituted with one or more optionally halogenated (C₁-C₆)alkyl and the alkyl group is optionally halogenated.

[0072] Suitable examples of such sulfonic acids are paratoluenesulfonicacid, methanesulfonic acid and trifluoromethanesulfonic acid, the latterbeing particularly preferred.

[0073] According to one preferred embodiment of the invention, anactivated derivative of the sulfonic acid is used. The term “activatedderivative” denotes a sulfonic acid in which the acid function —SO₃H isactivated, for example by formation of an anhydride bond or an —SO₃Clgroup.

[0074] One sulfonic acid derivative which is particularly advantageousis the symmetrical anhydride of trifluoromethanesulfonic acid, offormula (CF₃—SO₂)₂O.

[0075] When the sulfonic acid has the formula P—SO₃H above or is anactivated form of this acid, the disulfonate obtained after step ii)corresponds to formula IV:

[0076] in which A and P are as defined above.

[0077] The conditions of the esterification reaction will be readilydeveloped by those skilled in the art. These conditions depend inparticular on the nature of the esterifying agent. When the esterifyingagent is a sulfonic acid, a higher reaction temperature, of between 20and 100° C., may prove to be necessary. Conversely, starting with anactivated form of this acid, such as an anhydride or a sulfonylchloride, a lower temperature may be suitable. Generally, a temperatureof between −30° C. and 50° C. and preferably between −15° C. and 20° C.may suffice in this case.

[0078] The esterification is preferably carried out in a solvent.Suitable solvents are, in particular, optionally halogenated aliphatic,aromatic or cyclic hydrocarbons, such as those defined above. Mentionmay be made of carbon tetrachloride and dichloromethane. Dichloromethaneis particularly preferred. Ethers may also be used as solvent. Mentionwill be made, for example, of C₁-C₆ dialkyl ethers (diethyl ether anddiisopropyl ether), cyclic ethers (tetrahydrofuran and dioxane),dimethoxyethane and diethylene glycol dimethyl ether.

[0079] When the esterifying agent is an activated form of a sulfonicacid, it is desirable to introduce a base into the reaction medium.Examples of bases are N-methylmorpholine, triethylamine, tributylamine,diisopropylethylamine, dicyclohexylamine, N-methylpiperidine, pyridine,2,6-dimethylpyridine, 4-(1-pyrrolidinyl) pyridine, picoline,4-(N,N-dimethylamino)-pyridine, 2,6-di-t-butyl-4-methylpyridine,quinoline, N,N-dimethylaniline and N,N-diethylaniline.

[0080] Preferred bases which will be essentially selected are pyridineand 4-dimethylaminopyridine.

[0081] The reaction may also be performed in a two-phase mixture ofwater and of an organic solvent such as a haloaliphatic hydrocarbon (forexample carbon tetrachloride) . In this case, it is preferable to use anesterifying agent in anhydride form and to perform the process in thepresence of a water-soluble base such as KOH, NaOH or K₂CO₃, preferablyKOH.

[0082] The reaction of the sulfonic acid or the activated derivativethereof with the bromo diol III is stoichiometric. Nevertheless, it ispreferable to perform the process in the presence of an excess of theacid or the activated form thereof. Thus, a ratio of the acid,optionally in activated form, to the diol III of between 2 and 5 andbetter still between 2 and 3 is recommended.

[0083] When the reaction is performed in solution, the concentration ofthe reagents, which is not a critical parameter according to theinvention, may range between 0.1 and 10 mol/l and advantageously between1 and 5 mol/l.

[0084] Those skilled in the art may be inspired by the operatingconditions illustrated in J. Org. Chem., vol. 58, No. 7, 1993, 1945-1948and Tetrahedron Letters, vol. 31, No. 7, 985-988, 1990 for carrying outthe esterification.

[0085] The following step (iii) is a nucleophilic substitution. The twobromine atoms borne by the nuclei A are displaced with cyano groups bythe action of a suitable nucleophilic agent.

[0086] So as to perform this substitution, those skilled in the art mayuse any of the methods known in the art.

[0087] According to one preferred embodiment of the invention, thenucleophilic agent used is copper cyanide.

[0088] The molar ratio of the copper cyanide to the disulfonate ispreferably greater than 2 and may advantageously range between 2 and 4and preferably between 2 and 3.

[0089] The reaction is preferably carried out in a solvent. Examples ofsolvents which may be mentioned are amides such as formamide,dimethylformamide, dimethylacetamide, 2-N-methylpyrrolidinone andhexamethylphosphorylamide. Dimethylformamide is clearly preferred.Pyridine is also a suitable solvent. The reaction temperature isadvantageously maintained between 50 and 200° C., for example between 70and 190° C. and better still between 80 and 180° C.

[0090] A temperature which is more particularly suitable is between 100and 190° C.

[0091] The concentration of the reagents in the reaction mediumgenerally ranges between 0.1 and 10 mol/l, for example between 2 and 7mol/l.

[0092] The isolation of the nitrile involves decomposing theintermediate complex formed and trapping the excess cyanide.

[0093] The hydrolysis of the intermediate complex may be performedeither by the action of hydrated iron chloride or by the action ofaqueous ethylenediamine.

[0094] In the first case, the reaction medium is poured into an aqueous50-80% (g/ml) iron chloride solution containing concentratedhydrochloric acid. The resulting solution is heated at 40-80° C. untilthe complex has completely decomposed. The medium is then separated outby settling and extracted conventionally.

[0095] In the second case, the reaction medium is poured into an aqueousethylenediamine solution (ethylenediamine/water: 1/5-1/1 (v/v), forexample 1/3 ) and the mixture is then stirred vigorously. The medium isthen separated by settling of the phases and extracted in a manner whichis known per se.

[0096] Those skilled in the art may be inspired by the work of L.Friedman et al. published in J.O.C. 1961, 26, 1522, for isolating thenitrile.

[0097] Starting with the disulfonate of formula IV mentioned above, theproduct obtained at the end of this step is the nitrile of formula V:

[0098] in which A and P are as defined above and the position of thecyano group on the nucleus A is the same as that of the bromine incompound IV.

[0099] In the following step (iv), a cross-coupling of a phosphine offormula VI:

XPAr₁Ar₂   VI

[0100] in which X is a halogen or hydrogen atom and Ar₁ and Ar₂ are asdefined above, is carried out with the nitrile obtained in the abovestep, in the presence of a catalyst based on a transition metal.

[0101] This coupling leads directly to the expected compound of formulaI.

[0102] Examples of suitable catalysts are catalysts based on nickel,palladium, rhodium, ruthenium or platinum or on a mixture of thesemetals.

[0103] The preferred catalysts are nickel-based catalysts such as thosechosen from NiCl₂; NiBr₂; NiCl₂(dppp); NiCl₂(dppb); NiCl₂(dppf);NiCl₂(dppe); NiCl₂(PPh₃)₂; Ni(CO)₂(PPh₃)₂; Ni(PPh₃)₄ and Ni[P(PhO)₃]₄ inwhich dppe means (diphenylphosphino)ethane, dppp means(diphenylphosphino) propane, dppb means (diphenylphosphino) butane anddppf means (diphenylphosphino)ferrocenyl.

[0104] Among these catalysts, NiCl₂(dppe) is preferred.

[0105] The reaction is generally carried out at a temperature of from 50to 200° C. and preferably from 80 to 130° C.

[0106] The molar ratio of compound VI to the nitrile is at least 2. Itgenerally ranges between 2 and 4, for example between 2 and 3.

[0107] The amount of catalyst is preferably such that the molar ratio ofthe nitrile to the catalyst ranges between 5 and 100 and in particularbetween 5 and 80.

[0108] The reaction is preferably performed in a polar aprotic solventand in particular an amide such as those mentioned above. In this casealso, N,N-dimethylformamide is preferred. Nevertheless, other types ofpolar solvent may be used, such as (C₁-C₆)alkanols (ethanol) aromatichydrocarbons (toluene, xylene and benzene), ethers (dioxane) andacetonitrile.

[0109] The precise reaction conditions depend on the nature of thecompound of formula VI involved in the reaction.

[0110] When compound VI is HPAr₁Ar₂, the reaction is advantageouslyperformed in the presence of a base.

[0111] Bases that are particularly suitable are pyridine,4-dimethylaminopyridine, 2,6-di-tert-butylpyridine,1,8-diazabicyclo[5.4.0]undec-7-ene (DBU),1,5-diazabicyclo[4.3.0]non-5-ene (DBN) and1,4-diazabicyclo-[2.2.2]octane (DABCO or triethylenediamine). DABCO willadvantageously be used as base. In this case, it is preferred for themolar ratio of the nitrile to the catalyst to be between 5 and 20, forexample between 7 and 15.

[0112] When the compound of formula VI is halPAr₁Ar₂ in which hal is ahalogen atom, preferably Cl or Br (better still Cl), it is necessary toadd zinc to the reaction medium.

[0113] The amount of zinc is preferably such that the molar ratio of thezinc to the halPAr₁AR₂ ranges between 1 and 2 and preferably between 1.2and 1.7.

[0114] In this case, it is desirable to cool the reaction mixturecontaining the solvent, the nitrile and compound VI to a temperature ofbetween −10° C. and 20° C. throughout the addition of the zinc to thereaction medium. Then, the reaction takes place by heating to a suitabletemperature of between 50° C. and 200° C.

[0115] When the compound of formula VI is halPAr₁Ar₂, it is preferredfor the molar ratio of the nitrile to the catalyst to be between 40 and80, for example between 50 and 70.

[0116] For further details regarding the implementation of thesecoupling reactions, those skilled in the art will refer to D. Cai et al.J.O.C. 1994, 59, 7180 and D. J. Ager et al. Chem. Comm. 1997, 2359.

[0117] When A represents phenyl which is optionally substituted,preferably with (C₁-C₆)alkyl or (C₁-C₆)alkoxy, the compound obtainedafter step (iv) has the formula Ic:

[0118] in which Ar₁, Ar₂, S₁ and S₂ are as defined above for formulaIIa.

[0119] When A represents naphthyl, the compound obtained after step (iv)has the formula Ib:

[0120] in which Ar₁ and Ar₂ are as defined above.

[0121] The compounds of formula I are ligands capable of coordinating totransition metals such as ruthenium and rhodium. When combined withthese metals, the ligands form complexes that are useful in theasymmetric catalysis of enantioselective hydrogenation reactionsstarting with varied substrates such as β-keto esters, α-keto esters anddehydroamino acids.

[0122] The present invention moreover provides a process for convertingthe compounds of formula I (which contain two cyano functions) intocorresponding diaminomethyl compounds.

[0123] As a variant, it is possible to convert the two cyano functionsof the compounds of formula I into carboxylic acid, imine, hydroxymethylor amide functions.

[0124] The products resulting from these conversions are also ligandswhich may be used in asymmetric catalysis.

[0125] Thus, according to another of its aspects, the invention relatesto a process comprising, in addition to steps (i) to (iv) defined above,the step consisting in reducing the nitrile function of the compound offormula I by the action of a reducing agent so as to obtain a compoundof formula VII:

[0126] in which A, Ar₁ and Ar₂ are as defined above.

[0127] A suitable reducing agent is lithium aluminum hydride (LiAlH₄).

[0128] The invention is not intended to be limited to the use of thisparticular reducing agent.

[0129] The reaction is preferably carried out in a solvent or a mixtureof solvents.

[0130] When the reducing agent is LiAlH₄, the solvent advantageouslycomprises one or more aromatic hydrocarbons (such as benzene, toluene orxylene) mixed with one or more ethers.

[0131] Ethers which may be mentioned are C₁-C₆ alkyl ethers (diethylether and diisopropyl ether), cyclic ethers (dioxane andtetrahydrofuran), dimethoxyethane and diethylene glycol dimethyl ether.

[0132] Cyclic ethers such as tetrahydrofuran are preferred.

[0133] When the reducing agent is LiAlH₄, a mixture of toluene andtetrahydrofuran in proportions ranging between (v/v)70-50/30-50:toluene/tetrahydrofuran (for example 60/40:toluene/THF) willbe chosen more preferably.

[0134] The reduction may be carried out at a temperature of between 20°C. and 100° C. and preferably between 40° C. and 80° C.

[0135] A large excess of the reducing agent is usually used. Thus, themolar ratio of the reducing agent to the compound of formula I generallyranges between 1 and 30, for example between 2 and 20 and in particularbetween 5 and 18.

[0136] The concentration of the reagents in the medium is variable; itmay be maintained between 0.005 and 1 mol/l.

[0137] The compounds of formula VII obtained according to the process ofthe invention are novel and form another subject of the invention. Amongthese compounds, preference is given to those for which A representsnaphthyl, which correspond to the following formula:

[0138] in which Ar₁ and Ar₂ are as defined in claim 1.

[0139] A preferred group of these diamines consists of the compounds offormula VIIa in which Ar₁ and Ar₂ are independently chosen from phenyloptionally substituted with methyl or tert-butyl; and (C₅-C₆)cycloalkyloptionally substituted with methyl or tert-butyl.

[0140] Better still, preference is given to the compounds in which Ar₁and Ar₂ are identical and represent optionally substituted phenyl.

[0141] As a variant, the invention provides a process comprising, inaddition to steps (i) to (iv) defined above, the step consisting intreating the compound of formula I in a acidic medium or in basicmedium, so as to obtain the corresponding carboxylic acid of formulaVIII:

[0142] in which A, Ar₁ and Ar₂ are as defined above.

[0143] The conversion of a nitrile function into a carboxylic acidfunction is described in organic chemistry textbooks. Thus, thoseskilled in the art can readily determine the appropriate reactionconditions.

[0144] One simple way of performing the process consists in usingaqueous sodium hydroxide as hydrolysis agent.

[0145] The process of the invention may be carried out starting with anoptically active compound II with conservation of the chirality from thestart to the end of the synthesis.

[0146] With the aim of conserving the chirality, the esterification ofthe compound of formula III will be carried out under anhydrousconditions in the presence of suitable bases chosen fromN-methylmorpholine, triethylamine, tributylamine, diisopropylethamine,dicyclohexylamine, N-methylpiperidine, pyridine, 2,6-dimethylpyridine,4-(1-pyrrolidinyl)pyridine, picoline, 4-(N,N-dimethylamino)pyridine,2,6-di-t-butyl-4-methylpyridine, quinoline, N,N-dimethylaniline andN,N-diethylaniline.

[0147] Thus, starting with a (S)-2,2′-dihydroxy-1,1′-binaphthyl,(S)-6,6′-dibromo-2,2′-dihydroxy1,1′-binaphthyl and(S)-6,6′-dicyano-2,2′-bis(diarylphosphino)-1,1′-binaphthyl aresuccessively obtained.

[0148] The same process applied to (R)-2,2′-dihydroxy-1,1′-binaphthylgives (R)-6,6′-dicyano-2,2-bis(diarylphosphino)-1,1′-binaphthyl.

[0149] The optically active isomers of the compounds of formula II areconventionally isolated from the corresponding racemic mixtures. Anoptically active resolving agent is usually used to do this.

[0150] In the case of 1,1′-bis(2-naphthol), the enantiomers may beresolved by forming an inclusion complex with(R,R)-1,2-cyclohexanediamine, (R,R) or(S,S)-2,3-(+)-dimethoxy-N,N,N′,N′-tetramethylsuccinamide oralternatively (R,R) or(S,S)-2,3-(+)-N,N,N′,N′-tetramethyl-2,2′-dimethyl-1,3-dioxolane-trans-dicarboxamide.These methods have been described in the literature. Another way ofperforming the process consists in forming an inclusion complex of1′-bis(2-naphthol) with N-benzylcinchoninium chloride. Usingacetonitrile as solvent, only the complex with one of the enantiomersprecipitates, thus allowing the two enantiomers to be separated.Reference will be made in this respect to the studies by D. Caipublished in Tetrahedron Letters, vol. 36, No. 44, 7991-7994, 1995.

[0151] As a variant, it is possible, in order to prepare an opticallyactive compound of formula I, to carry out step a) starting with aracemic diol of formula II, to resolve the bromo derivative obtained offormula III and then to continue the synthesis starting with theappropriate optically active bromo compound III.

[0152] The difunctional ligands obtained according to the processes ofthe invention may be used in the preparation of metal complexes intendedfor the asymmetric catalysis of hydrogenation reactions, hydrosilylationreactions, hydroboration reactions of unsaturated compounds, epoxidationreactions of allylic alcohols, vicinal hydroxylation reactions,hydrovinylation reactions, hydroformylation reactions, cyclopropanationreactions, isomerization reactions of olefins, polymerization reactionsof propylene, addition reactions of organometallic compounds toaldehydes, allylic alkylation reactions, reactions of aldol type,Diels-Alder reactions and, in general, reactions for the formation ofC—C bonds (such as allylic substitutions or Grignard cross-couplings).

[0153] According to one preferred embodiment of the invention, thecomplexes are used for the hydrogenation of C═O, C═C and C═N bonds.

[0154] The complexes which may be used in reactions of this type arerhodium, ruthenium, palladium, platinum, iridium, cobalt, nickel orrhenium complexes, preferably rhodium, ruthenium, iridium, palladium andplatinum complexes. Even more advantageously, rhodium, ruthenium oriridium complexes are used.

[0155] Specific examples of said complexes of the present invention aregiven below, with no limiting nature.

[0156] In the following formulae, P represents a ligand according to theinvention.

[0157] A preferred group of the rhodium and iridium complexes is definedby the formula:

[MeLig₂P]Y_(I)   IX

[0158] in which:

[0159] P represents a ligand according to the invention;

[0160] Y_(I) represents a coordinating anionic ligand;

[0161] Me represents iridium or rhodium; and

[0162] Lig represents a neutral ligand.

[0163] Among these compounds, those in which:

[0164] Lig represents an olefin containing from 2 to 12 carbon atoms;

[0165] Y_(I) represents a PF₆ ⁻, PCl₆ ⁻, BF₄ ⁻, BCl₄ ⁻, SbF₆ ⁻, SbCl₆ ⁻,BPh₄ ⁻, ClO₄ ⁻, CN⁻, CF₃SO₃ ⁻ or halogen, preferably Cl⁻ or Br⁻, anion,a 1,3-diketonate, alkylcarboxylate or haloalkylcarboxylate anion with alower alkyl (preferably C₁-C₆) radical, a phenylcarboxylate or phenoxideanion in which the benzene ring may be substituted with lower alkyl(preferably C₁-C₆) radicals and/or halogen atoms,

[0166] are particularly preferred.

[0167] In formula IX, Lig₂ may represent two Lig ligands as definedabove or a bidentate ligand such as a linear or cyclic, polyunsaturatedbidentate ligand comprising at least two unsaturations.

[0168] It is preferred according to the invention for Lig₂ to represent1,5-cyclooctadiene, norbornadiene or for Lig to represent ethylene.

[0169] The expression “lower alkyl radicals” generally means a linear orbranched alkyl radical containing from 1 to 4 carbon atoms.

[0170] Other iridium complexes are those of formula:

[IrLigP]Y_(I)   X

[0171] in which Lig, P and Y_(I) are as defined for formula IX.

[0172] A preferred group of ruthenium complexes consists of thecompounds of formula:

[RuY_(I) ¹Y_(I) ²P]  XI

[0173] in which:

[0174] P represents a ligand according to the invention;

[0175] Y_(I) ¹ and Y_(I) ², which may be identical or different,represent a PF₆ ⁻, PCl₆ ⁻, BF₄ ⁻, BCl₄ ⁻, SbF₆ ⁻, SbCl₆ ⁻, BPh₄ ⁻, ClO₄⁻ or CF₃SO₃ ⁻ anion, a halogen atom, more particularly chlorine orbromine, or a carboxylate anion, preferably acetate or trifluoroacetate.

[0176] Other ruthenium complexes are those corresponding to formula XIIbelow:

[RuY_(I) ³arPY_(I) ⁴]  XII

[0177] in which:

[0178] P represents a ligand according to the invention;

[0179] ar represents benzene, p-methylisopropylbenzene orhexamethylbenzene;

[0180] Y_(I) ³ represents a halogen atom, preferably chlorine orbromine;

[0181] Y_(I) ⁴ represents an anion, preferably a PF₆ ⁻, PCl₆ ⁻, BF₄ ⁻,BCl₄ ⁻, SbF₆ ⁻, SbCl₆ ⁻, BPh₄ ⁻, ClO₄ ⁻ or CF₃SO₃ ⁻ anion.

[0182] It is also possible to use in the process of the inventionpalladium-based and platinum-based complexes.

[0183] As more specific examples of said complexes, mention may be made,inter alia, of Pd(hal)₂P and Pt(hal)₂P in which P represents a ligandaccording to the invention and hal represents halogen such as, forexample, chlorine.

[0184] The complexes comprising a ligand according to the invention andthe transition metal may be prepared according to the known processesdescribed in the literature.

[0185] The complexes are generally prepared from a precatalyst whosenature varies according to the transition metal selected.

[0186] In the case of rhodium complexes, the precatalyst is, forexample, one of the following compounds: [Rh^(I)(CO)₂Cl]₂;[Rh^(I)(COD)₂Cl]₂ in which COD denotes cyclooctadiene; orRh^(I)(acac)(CO)₂ in which acac denotes acetylacetonate.

[0187] In the case of ruthenium complexes, precatalysts that areparticularly suitable arebis(2-methylallyl)-cycloocta-1,5-dieneruthenium and [RuCl₂(benzene)]₂.Mention may also be made of Ru(COD) (η³-(CH₂)₂CHCH₃)₂ .

[0188] By way of example, starting withbis(2-methylallyl)-cycloocta-1,5-dieneruthenium, a solution orsuspension is prepared containing the metallic precatalyst, a ligand anda fully degassed solvent such as acetone (the ligand concentration inthe solution or suspension ranging between 0.001 and 1 mol/l), to whichis added a methanolic hydrogen bromide solution. The ratio of theruthenium to the bromine advantageously ranges between 1:1 and 1:4 andpreferably between 1:2 and 1:3. The molar ratio of the ligand to thetransition metal is itself about 1. It may be between 0.8 and 1.2.

[0189] When the precatalyst is [RuCl₂(benzene)]₂, the complex isprepared by mixing the precatalyst, the ligand and an organic solventand optionally maintaining a temperature of between 15° C. and 150° C.for 1 minute to 24 hours, preferably 30° C. to 120° C. for 10 minutes to5 hours.

[0190] Solvents which may be mentioned are aromatic hydrocarbons (suchas benzene, toluene and xylene), amides (such as formamide,dimethylformamide, dimethyl-acetamide, 2-N-methylpyrrolidinone orhexamethyl-phosphorylamide) and alcohols (such as ethanol, methanol,n-propanol and isopropanol), and mixtures thereof.

[0191] Preferably, when the solvent is an amide, in particulardimethylformamide, the mixture of the ligand, the precatalyst and thesolvent is heated to between 80° C. and 120° C.

[0192] As a variant, when the solvent is a mixture of an aromatichydrocarbon (such as benzene) with an alcohol (such as ethanol), thereaction medium is heated to a temperature of between 30° C. and 70° C.

[0193] The catalyst is then recovered according to the conventionaltechniques (filtration or crystallization) and used in asymmetricreactions. Nevertheless, the reaction which needs to be catalyzed withthe complex thus prepared may be carried out without intermediateisolation of the catalyst complex.

[0194] In the text hereinbelow, the case of hydrogenation is describedin detail.

[0195] The unsaturated substrate, dissolved in a solvent comprising thecatalyst, is placed under a pressure of hydrogen.

[0196] The hydrogenation is carried out, for example, at a pressureranging between 1.5 bar and 100 bar, and at a temperature of between 20°C. and 100° C.

[0197] The exact implementation conditions depend on the nature of thesubstrate which needs to be hydrogenated. Nevertheless, in the generalcase, a pressure of from 20 bar to 80 bar and preferably from 40 bar to60 bar, and a temperature of from 30° C. to 70° C., are particularlysuitable.

[0198] The reaction medium may consist of the reaction medium in whichthe catalyst was obtained. The hydrogenation reaction then takes placein situ.

[0199] As a variant, the catalyst is isolated from the reaction mediumin which it was obtained. In this case, the reaction medium for thehydrogenation reaction consists of one or more solvents, chosen inparticular from C₁-C₅ aliphatic alcohols such as methanol or propanoland an amide as defined above, for example dimethylformamide, optionallymixed with benzene.

[0200] When the hydrogenation reaction takes place in situ, it isdesirable to add to the reaction medium one or more solvents chosen fromthose mentioned above, and more particularly one or more aliphaticalcohols.

[0201] According to one preferred embodiment, fully degassed methanoland the substrate are added to the reaction medium containing thecomplex. The amount of methanol, or more generally of solvent, which maybe added is such that the concentration of the substrate in thehydrogenation reaction medium is between 1×10⁻³ and 10 mol/l andpreferably between 0.01 and 1 mol/l.

[0202] The molar ratio of the substrate to the catalyst generally rangesfrom 1/100 to 1/100 000 and preferably from 1/20 to 1/2 000. This ratiois, for example, 1/1 000.

[0203] The rhodium complexes prepared from the ligands of the inventionare more especially suitable for the asymmetric catalysis ofisomerization reactions of olefins.

[0204] The ruthenium complexes prepared from the ligands of theinvention are more especially suitable for the asymmetric catalysis ofhydrogenation reaction of carbonyl bonds, of C═C bonds and of C═N bonds.

[0205] As regards the hydrogenation of double bonds, the suitablesubstrates are of the type such as α,β-unsaturated carboxylic acidand/or α,β-unsaturated carboxylic acid derivatives. These substrates aredescribed in EP 95943260.0.

[0206] The α,βunsaturated carboxylic acid and/or the derivative thereofcorresponds more particularly to formula A:

[0207] in which:

[0208] R₁, R₂, R₃ and R₄ represent a hydrogen atom or anyhydrocarbon-based group, provided that:

[0209] if R₁ is different than R₂ and other than a hydrogen atom, thenR₃ can be any hydrocarbon-based group or functional group denoted by R,

[0210] if R₁ or R₂ represents a hydrogen atom and if R₁ is other thanR₂, then R₃ is other than a hydrogen atom and other than —COOR₄,

[0211] if R₁ is identical to R₂ and represents any hydrocarbon-basedgroup or functional group denoted by R, then R₃ is other than —CH—(R)₂,and other than —COOR₄,

[0212] one of the groups R₁, R₂ and R₃ possibly representing afunctional group.

[0213] A specific example which may be mentioned, inter alia, is2-methyl-2-butenoic acid.

[0214] A first group of preferred substrates is formed by substitutedacrylic acids that are precursors of amino acids and/or derivatives.

[0215] The expression “substituted acrylic acids” means the set ofcompounds whose formula is derived from that of acrylic acid bysubstituting not more than two of the hydrogen atoms borne by theethylenic carbon atoms with a hydrocarbon-based group or with afunctional group.

[0216] They may be symbolized by the following chemical formula:

[0217] in which:

[0218] R₉ and R′₉, which may be identical or different, represent ahydrogen atom, a linear or branched alkyl group containing from 1 to 12carbon atoms, a phenyl group or an acyl group containing from 2 to 12carbon atoms, and preferably an acetyl or benzoyl group,

[0219] R₈ represents a hydrogen atom, an alkyl group containing from 1to 12 carbon atoms, a cycloalkyl radical containing from 3 to 8 carbonatoms, an arylalkyl radical containing from 6 to 12 carbon atoms, anaryl radical containing from 6 to 12 carbon atoms or a heterocyclicradical containing from 4 to 7 carbon atoms,

[0220] R₁₀ represents a hydrogen atom or a linear or branched alkylgroup containing from 1 to 4 carbon atoms.

[0221] Mention may be made more particularly of:

[0222] methyl α-acetamidocinnamate,

[0223] methyl acetamidoacrylate,

[0224] benzamidocinnamic acid,

[0225] α-acetamidocinnamic acid.

[0226] A second preferred group of substrates consists of itaconic acidand derivatives thereof of formula:

[0227] in which:

[0228] R₁₁ and R₁₂, which may be identical or different, represent ahydrogen atom, a linear or branched alkyl group containing from 1 to 12carbon atoms, a cycloalkyl radical containing from 3 to 8 carbon atoms,an arylalkyl radical containing from 6 to 12 carbon atoms, an arylradical containing 6 to 12 carbon atoms a heterocyclic radicalcontaining from 4 to 7 carbon atoms,

[0229] R₁₀ and R′₁₀, which may be identical or different, represent ahydrogen atom or a linear or branched alkyl group containing from 1 to 4carbon atoms.

[0230] As more specific examples, mention may be made in particular ofitaconic acid and dimethyl itaconate.

[0231] A third preferred group of substrates is defined by formula A3:

[0232] in which:

[0233] R″₁₀ represents a hydrogen atom or a linear or branched alkylgroup containing from 1 to 4 carbon atoms,

[0234] R₁₃ represents a phenyl or naphthyl group optionally bearing oneor more substituents.

[0235] Specific examples which may be mentioned are the substratesleading by hydrogenation to 2-(3-benzoyl-phenyl)propionic acid(Ketoprofen®), 2-(4-isobutyl-phenyl)propionic acid (Ibuprofen®) and2-(5-methoxy-naphthyl)propionic acid (Naproxen®)

[0236] As regards the hydrogenation of carbonyl bonds, the appropriatesubstrates of ketone type correspond more preferably to formula B:

[0237] in which:

[0238] R₅ is different than R₆,

[0239] R₅ and R₆ represent a hydrocarbon-based radical containing from 1to 30 carbon atoms optionally comprising one or more functional groups,

[0240] R₅ and R₆ can form a ring optionally comprising another heteroatom,

[0241] Z is or comprises an oxygen or nitrogen hetero atom or afunctional group comprising at least one of these hetero atoms.

[0242] These compounds are specifically described in FR 96/08060 and EP97930607.3.

[0243] A first preferred group of such keto substrates has the formulaB1:

[0244] in which:

[0245] R₅ is different than R₆, the radicals R₅ and R₆ represent ahydrocarbon-based radical containing from 1 to 30 carbon atomsoptionally comprising another ketone and/or acid, ester, thioacid orthioester function;

[0246] R₅ and R₆ can form a substituted or unsubstituted carbocyclic orheterocyclic ring containing 5 or 6 atoms.

[0247] Among these compounds, the ones that are most particularlypreferred are the ketones chosen from:

[0248] methyl phenyl ketone,

[0249] isopropyl phenyl ketone,

[0250] cyclopropyl phenyl ketone,

[0251] allyl phenyl ketone,

[0252] p-methylphenyl methyl ketone,

[0253] benzyl phenyl ketone,

[0254] phenyl triphenylmethyl ketone,

[0255] o-bromoacetophenone,

[0256] α-bromoacetone,

[0257] α-dibromoacetone,

[0258] α-chloroacetone,

[0259] α-dichloroacetone,

[0260] α-trichloroacetone,

[0261] 1-chloro-3,3-dichloroacetone

[0262] 1-chloro-2-oxobutane,

[0263] 1-fluoro-2-oxobutane,

[0264] 1-chloro-3-methyl-2-butanone,

[0265] α-chloroacetophenone,

[0266] 1-chloro-3-phenylacetone,

[0267] α-methylaminoacetone,

[0268] α-dimethylaminoacetone,

[0269] 1-butylamino-2-oxopropane,

[0270] 1-dibutylamino-2-oxopropane,

[0271] 1-methylamino-2-oxobutane,

[0272] 1-dimethylamino-2-oxobutane,

[0273] 1-dimethylamino-3-methyl-2-oxobutane,

[0274] 1-dimethylamino-2-oxopentane,

[0275] α-dimethylaminoacetophenone,

[0276] α-hydroxyacetone,

[0277] 1-hydroxy-3-methyl-2-butanone,

[0278] 1-hydroxy-2-oxobutane,

[0279] 1-hydroxy-2-oxopentane,

[0280] 1-hydroxy-2-oxohexane,

[0281] 1-hydroxy-2-oxo-3-methylbutane,

[0282] α-hydroxyacetophenone,

[0283] 1-hydroxy-3-phenylacetone,

[0284] α-methoxyacetone,

[0285] α-methoxyacetophenone,

[0286] α-ethoxyacetone,

[0287] α-butoxyacetophenone,

[0288] α-chloro-p-methoxyacetophenone,

[0289] α-naphthenone,

[0290] 1-ethoxy-2-oxobutane,

[0291] 1-butoxy-2-oxobutane,

[0292] α-dimethoxyphosphorylacetone,

[0293] 3-oxotetrahydrothiophene.

[0294] Substrates of aldehyde/ketone type containing a second carbonylgroup in an α, β, γ or δ position relative to the first carbonyl groupare also particularly suitable in the context of the invention. Examplesof such diketo compounds are:

[0295] α-formylacetone,

[0296] diacetyl,

[0297] 3,4-dioxohexane,

[0298] 4,5-dioxooctane,

[0299] 1-phenyl-1,2-dioxopropane,

[0300] 1-phenyl-2,3-dioxobutane,

[0301] diphenylglyoxal,

[0302] p-methoxydiphenylglyoxal,

[0303] 1,2-cyclopentanedione,

[0304] 1,2-cyclohexanedione,

[0305] acetylacetone,

[0306] 3,5-heptanedione,

[0307] 4,6-nonanedione,

[0308] 5,7-undecadione,

[0309] 2,4-hexanedione,

[0310] 2,4-heptanedione,

[0311] 2,4-octanedione,

[0312] 2,4-nonanedione,

[0313] 3,5-nonanedione,

[0314] 3,5-decanedione,

[0315] 2,4-dodecanedione,

[0316] 1-phenyl-1,3-butanedione,

[0317] 1-phenyl-1,3-pentanedione,

[0318] 1-phenyl-1,3-hexanedione,

[0319] 1-phenyl-1,3-heptanedione,

[0320] 3-methyl-2,4-pentanedione,

[0321] 1,3-diphenyl-1,3-propanedione,

[0322] 1,5-diphenyl-2,4-pentanedione,

[0323] 1,3-bis(trifluoromethyl)-1,3-propanedione,

[0324] 3-chloro-2,4-pentanedione,

[0325] 1,5-dichloro-2,4-pentanedione,

[0326] 1,5-dihydroxy-2,4-pentanedione,

[0327] 1,5-dibenzyloxy-2,4-pentanedione,

[0328] 1,5-diamino-2,4-pentanedione,

[0329] 1,5-bis(methylamino)-2,4-pentanedione,

[0330] 1,5-bis(dimethylamino)-2,4-pentanedione,

[0331] methyl 3,5-dioxohexanoate,

[0332] 3-carbomethoxy-2,4-pentanedione,

[0333] 3-carboethoxy-2,4-pentanedione,

[0334] 1,3-cyclopentanedione,

[0335] 1,3-cyclohexanedione,

[0336] 1,3-cycloheptanedione,

[0337] 5-carboethoxy-1,3-cyclopentanedione,

[0338] 2-acetyl-1-cyclopentanone,

[0339] 2-acetyl-1-cyclohexanone.

[0340] As other substrates that are particularly suitable, mention maybe made of keto acids or derivatives thereof and keto thioacids orderivatives thereof with a functional group (acid, ester, thioacid orthioester) in an α, β, γ or δ position relative to the carbonyl group.Examples of these are:

[0341] 2-acetylbenzoic acid,

[0342] pyruvic acid,

[0343] 2-oxobutanoic acid,

[0344] 3-methyl-2-oxobutanoic acid,

[0345] phenylglyoxylic acid,

[0346] phenylpyruvic acid,

[0347] p-methoxyphenylpyruvic acid,

[0348] 3,4-dimethoxyphenylpyruvic acid,

[0349] methyl acetoacetate,

[0350] ethyl acetoacetate,

[0351] n-propyl acetoacetate,

[0352] isopropyl acetoacetate,

[0353] n-butyl acetoacetate,

[0354] t-butyl acetoacetate,

[0355] n-pentyl acetoacetate,

[0356] n-hexyl acetoacetate,

[0357] n-heptyl acetoacetate,

[0358] n-octyl acetoacetate,

[0359] methyl 3-oxopentanoate,

[0360] methyl 3-oxohexanoate,

[0361] methyl 3-oxohexanoate,

[0362] ethyl 3-oxooctanoate,

[0363] ethyl 3-oxononanoate,

[0364] ethyl 3-oxodecanoate,

[0365] ethyl 3-oxoundecanoate,

[0366] ethyl 3-oxo-3-phenylpropanoate,

[0367] ethyl 4-phenyl-3-oxobutanoate,

[0368] methyl 5-phenyl-3-oxopentanoate,

[0369] ethyl 3-oxo-3-p-methoxyphenylpropanoate,

[0370] methyl 4-chloroacetoacetate,

[0371] ethyl 4-chloroacetoacetate,

[0372] methyl 4-fluoroacetoacetate,

[0373] ethyl 3-trifluoromethyl-3-oxopropanoate,

[0374] ethyl 4-hydroxy-3-oxobutanoate,

[0375] methyl 4-methoxyacetoacetate,

[0376] methyl 4-tert-butoxyacetoacetate,

[0377] methyl 4-benzyloxy-3-oxobutanoate,

[0378] ethyl 4-benzyloxy-3-oxobutanoate,

[0379] methyl 4-amino-3-oxobutanoate,

[0380] ethyl 3-methylamino-3-oxobutanoate,

[0381] methyl 4-dimethylamino-3-oxobutanoate,

[0382] ethyl 4-dimethylamino-3-oxobutanoate,

[0383] methyl 2-methylacetoacetate,

[0384] ethyl 2-methylacetoacetate,

[0385] ethyl 2-chloroacetoacetate,

[0386] diethyl 2-acetylsuccinate,

[0387] diethyl 2-acetylglutarate,

[0388] dimethyl acetylmalonate,

[0389] thiomethyl acetoacetate,

[0390] thioethyl acetoacetate,

[0391] thiophenyl acetoacetate,

[0392] methyl pyruvate,

[0393] ethyl 3-methyl-2-oxobutanoate,

[0394] ethyl phenylglyoxolate,

[0395] methyl phenylpyruvate,

[0396] ethyl phenylpyruvate,

[0397] 3-oxobutanoic dimethylamide,

[0398] 3-oxobutanoic benzylamide,

[0399] 2-carboethoxycyclopentanone,

[0400] 2-carboethoxycyclohexanone,

[0401] ketopentalacetone,

[0402] 4-oxopentanoic acid,

[0403] 4-oxohexanoic acid,

[0404] 4-oxoheptanoic acid,

[0405] 4-oxodecanoic acid,

[0406] 4-oxododecanoic acid,

[0407] 4-phenyl-4-oxybutyric acid,

[0408] 4-p-methoxyphenyl-4-oxobutyric acid,

[0409] 4-(3,4-dimethoxyphenyl)-4-oxobutyric acid,

[0410] 4-(3,4,5-trimethoxyphenyl)-4-oxobutyric acid,

[0411] 4-p-chlorophenyl-4-oxybutyric acid,

[0412] 4-phenyl-4-oxobutyric acid.

[0413] It should be noted that when a γ-keto acid or derivative needs tobe asymmetrically hydrogenated, the product obtained is generally aγ-butyrolactone derivative and, in the case of a δ-keto acid, it is avalerolactone derivative.

[0414] Other examples of ketones which may be mentioned, inter alia, arethe following monocyclic or polycyclic, saturated or unsaturated cyclicketo compounds:

[0415] in which R represents a phenyl which is unsubstituted orsubstituted with alkyl or alkoxy radicals or a halogen atom; or Rrepresents an alkyl or cycloalkyl group which is unsubstituted orsubstituted with alkyl or alkoxy radicals or a halogen atom, a hydroxyl,ether or amine group; or R represents a halogen atom or a hydroxyl,alkoxy or amine group.

[0416] Ketones of steroid type may also be used (for example3-cholestanone or 5-cholesten-3-one).

[0417] Other keto substrates which may be mentioned are the compounds offormula B2:

[0418] in which:

[0419] R₅, which is other than R₆, have the meaning given above,

[0420] R₇ represents:

[0421] a hydrogen atom,

[0422] a hydroxyl group,

[0423] a group OR₁₇,

[0424] a hydrocarbon radical R₁₇,

[0425] a group of formula

[0426] a group of formula

[0427] with R₁₄, R₁₅, R₁₆ and R₁₇ which represent a hydrogen atom or ahydrocarbon-based group containing from 1 to 30 carbon atoms.

[0428] Examples of compounds of formula B2 are:

[0429] N-alkylketoimines, such as:

[0430] N-isobutyl-2-iminopropane

[0431] N-isobutyl-1-methoxy-2-iminopropane

[0432] N-arylalkylketoimines, such as:

[0433] N-benzyl-1-imino-1-(phenyl)ethane

[0434] N-benzyl-1-imino-1-(4-methoxyphenyl)ethane

[0435] N-benzyl-1-imino-1-(2-methoxyphenyl)ethane

[0436] N-arylketoimines, such as:

[0437] N-phenyl-2-iminopentane

[0438] N-(2,6-dimethylphenyl)-2-iminopentane

[0439] N-(2,4,6-trimethylphenyl)-2-iminopentane

[0440] N-phenyl-1-imino-1-phenylethane

[0441] N-phenyl-1-methoxy-2-iminopropane

[0442] N-(2,6-dimethylphenyl)-1-methoxy-2-iminopropane

[0443] N-(2-methyl-6-ethylphenyl)-1-methoxy-2-iminopropane

[0444] compounds of hydrazone type, optionally N-acylated orN-benzoylated:

[0445] 1-cyclohexyl-1-(2-benzoylhydrazono)ethane,

[0446] 1-phenyl-1-(2-benzoylhydrazono)ethane,

[0447] 1-p-methoxyphenyl-1-(2-benzoylhydrazono)ethane,

[0448] 1-p-ethoxyphenyl-1-(2-benzoylhydrazono)ethane,

[0449] 1-p-nitrophenyl-1-(2-benzoylhydrazono)ethane,

[0450] 1-p-bromophenyl-1-(2-benzoylhydrazono)ethane,

[0451] 1-p-carboethoxyphenyl-1-(2-benzoylhydrazono)ethane,

[0452] 1,2-diphenyl-1-(2-benzoylhydrazono)ethane,

[0453] 3-methyl-2-(2-p-dimethylaminobenzoylhydrazono)butane,

[0454] 1-phenyl-1-(2-p-methoxybenzoylhydrazono)ethane,

[0455] 1-phenyl-1-(2-p-dimethylaminobenzoylhydrazono)ethane,

[0456] ethyl 2-(2-benzoylhydrazono)propionate,

[0457] methyl 2-(2-benzoylhydrazono)butyrate,

[0458] methyl 2-(2-benzoylhydrazono)valerate,

[0459] methyl 2-phenyl-2-(2-benzoylhydrazono)acetate.

[0460] Other starting substrates are semicarbazones and cyclic ketoimines containing an endocyclic or exocyclic bond, such as:

[0461] According to one particularly preferred embodiment of theinvention, the substrate is a β-keto ester (such as methyl acetoacetateor methyl 3-oxovalerate), an α-keto ester (such as methyl benzoylformateor methyl pyruvate), a ketone (such as acetophenone), an olefin, anunsaturated amino acid or a derivative thereof (in particular an esterthereof).

[0462] The complexes obtained from the ligands of formula I and thederivatives thereof give, in particular, good enantioselectivity inhydrogenation reactions.

[0463] More particularly, the ruthenium complexes prepared from theligands obtained according to the process of the invention are suitablefor the asymmetric catalysis of hydrogenation reactions of the C═O bondsof β-keto esters.

[0464] The ruthenium complexes and ligands of formula VII areparticularly suitable for the asymmetric catalysis of hydrogenationreactions of the C═O bonds of ketones.

[0465] Thus, according to another of its aspects, the invention relatesto the use of a compound of formula I or of formula VII or of formulaVIII for the preparation of a metal complex intended for asymmetriccatalysis, and more especially a ruthenium, iridium or rhodium complex.

[0466] The use of a ligand of formula VII for the preparation of a metalcomplex and more specifically a ruthenium complex, intended for theasymmetric catalysis of hydrogenation reactions of ketones, forms apreferred subject of the invention.

[0467] The examples which follow illustrate the invention morespecifically.

PREPARATION 1 Preparation of(S)-6,6′-dibromo-2,2′-dihydroxy-1,1′-binaphthyl

[0468] 7.7 g (26.9 mmol) of (S)-2,2′-dihydroxy-1,1′-binaphthyl aredissolved in 145 ml of dichloromethane. The solution is cooled to −75°C. and 3.66 ml of Br₂ (71.7 mmol) are then added dropwise over 30minutes with constant stirring. The solution is stirred for a further 2and a half hours and then cooled to room temperature. After addition of180 ml of sodium bisulfite (10% by mass), the organic phase is washedwith saturated NaCl solution and dried over Na₂SO₄. After evaporatingoff the solvent, the solid obtained is recrystallized from atoluene/cyclohexane mixture at 80° C. to give 9.8 g (22 mmol, 82% yield)of expected product.

[0469] The optical rotation as measured on a Perkin-Elmer-241polarimeter (I=10 cm, 25° C., concentration c in g/dm³) is 124.3 atc=1.015 and 578 nm.

[0470] For the preparation of the dibromo derivative of the title,reference may be made to G. Dotsevi et al., J. Am. Chem. Soc., 1979,101, 3035.

PREPARATION 2 Preparation of(S)-6,6′-dibromo-2,2′-bis(trifloromethanesulfonyloxy)-1,1′-binaphthyl

[0471] 9.52 g (21.4 mmol) of(S)-6,6′-dibromo-2,2′-dihydroxy-1,1′-binaphthyl are dissolved in amixture of 40 ml of CH₂Cl₂ and 5.4 ml of pyridine. After cooling themixture to 0° C., 8.7 ml (14.5 g, 51.5 mmol) of triflic anhydride((CF₃—SO₂)₂O) are added slowly. After stirring for 6 h, the solvent isevaporated off and the reaction mass is dissolved in 100 ml of ethylacetate. After washing with aqueous 5% HCl solution, saturated NaHCO₃solution and saturated NaCl solution, the organic phase is dried overNa₂SO₄ and the solvent is then evaporated off under reduced pressure.The yellow oil is purified by chromatography on silica (CH₂Cl₂) to give12.5 g (17.7 mmol, 83% yield) of expected product.

[0472] [α]_(D)=151.3° (c=1.005, THF), the optical rotation beingmeasured under the same conditions as in Preparation 1, but at thewavelength corresponding to the D line of sodium.

[0473] For the preparation of the title compound, reference also be madeto the studies by M. Vondenhof Tetrahedron Letters, 1990, 31, 985.

PREPARATION 3 Preparation of(S)-6,6′-dibromo-2,2-bis(trifluoromethanesulfonyloxy)-1,1′-binaphthyl

[0474] As a variant, the title compound may be prepared from(R)-6,6′-dibromo-2,2′-dihydroxy-1,1′-binaphthyl according to theprocedure described below.

[0475] 10.0 g (22.52 mmol) of(R)-6,6′-dibromo-2,2′-dihydroxy-1,1′-binaphthyl are dissolved in asolution of 6.3 g (0.11 mol) of KOH in 300 ml of degased water. Themixture is cooled to 0° C. and a solution of 11.4 ml (19.1 g, 68 mmol)of triflic anhydride in 200 ml of CCl₄ is then added over 45 minutessuch that the temperature does not exceed 10° C. After stirring for 30min, 300 ml of CH₂Cl₂ are added. The organic phase is washed with waterand then dried over MgSO₄. 15.89 g of crude product are then purified bychromatography on silica (1/1 CH₂Cl₂/cyclohexane) to give 12.94 g (18.27mmol, 81% yield) of pure product.

[0476] [α]_(D)=153.2° (c=0.945, THF), the optical rotation beingmeasured under the same conditions as in Preparation 1, but at thewavelength corresponding to the D line of sodium.

[0477]¹H NMR (CDCl₃, 200 MHz): δ (ppm): 7.07 (d(J_(H-H)=7.07), CH, 2H);7.48 (dd(J¹ _(H-H)=9.05; J² _(H-H)=1.94), CH, 2H); 7.62(d(J_(H-H)=9.11), CH, 2H); p 8.06 (d(J_(H-H)=9.13), CH, 2H); 8.18 (d(J_(H-H)=1.90), CH, 2H).

[0478] C NMR (CDCl₃, 200 MHz); δ (ppm)=118.1 (Cq(J_(C-F)=320)); 120.2(Cq); 120.7 (CH); 122.0 (Cq); 123.4 (Cq); 128.2 (CH); 130.5 (CH); 131.4(CH); 131.6 (Cq); 131.7 (CH); 133.4 (Cq).

PREPARATION 4 Preparation of(S)-6,6′-dicyano-2,2′-bis(trifluoromethanesulfonyloxy)-1,1′-binaphthyl

[0479] 12.5 g (17.7 mmol) of the compound prepared in Preparation 2 and3.5 g (38.8 mmol) of CuCN are stirred at 180° C. in 20 ml ofN-methylpyrrolidone for 4 h. After cooling to room temperature, theblack suspension is poured into a solution of 15 ml of diaminoethane in35 ml of water. The solution is extracted several times with 30 ml ofCH₂Cl₂ and the organic phase is washed with aqueous 10% KCN solution andsaturated NaCl solution. After drying over Na₂SO₄, the solvent isevaporated off under reduced pressure. The black oil thus obtained ispurified by chromatography on silica (9/1 CH₂Cl₂/cyclohexane) to give6.5 g (10.8 mmol, 61% yield) of pure product.

[0480] [α]_(D)=−171.7° (c=1.15, THF), the optical rotation beingmeasured under the same conditions as in Preparation 1, but at thewavelength corresponding to the D line of sodium.

[0481]¹H NMR (CDCl₃, 200 MHz); δ (ppm)=7.30 (d(J_(H-H)=9.81), CH, 2H);7.59 (dd(J¹ _(H-H)=8.82, J² _(H-H)=1.65), CH, 2H); 7.78(d(J_(H-H)=9.11), CH, 2H); 8.29 (d(J_(H-H)8.09), CH, 2H); 8.46(d(J_(H-H)=1.29), CH, 2H).

[0482]¹³C NMR (CDCl₃, 200 MHz): δ (ppm)=111.7 (CN); 118.0 (Cq); 118.1(Cq(J_(C-F)=320)); 121.16 (CH); 123.3 (Cq); 127.7 (CH); 128.9 (CH);131.4 (Cq); 133.2 (CH); 134.4 (Cq); 134.5 (CH); 147.4 (Cq).

[0483] For the preparation of the title compound, those skilled in theart may refer to the studies by Friedman et al., J. Org. Chem. 1961, 26,2522 and M. S. Neuman et al., J. Org. Chem., 1961, 26, 2525.

EXAMPLE 1 Preparation of (S)-6,6′-dicyano-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (I: A=phenyl; Ar₁=Ar₂=phenyl)

[0484] A solution of NiCl₂dppe (371 mg, 0.7 mmol) and ofdiphenylphosphine (3 ml, 17 mmol) in 14 ml of DMF (anhydrous anddegased) is heated for 30 minutes at 100° C. in a 100 ml three-neckedround-bottomed flask on which is mounted an argon inlet.(S)-6,6′-Dicyano-2,2′-bis(trifluoromethanesulfonyloxy)-1,1′-binaphthyl(4.4 g, 7.4 mmol) and DABCO (3.375 g, 30 mmol) dissolved in 20 ml of DMFare added dropwise. The reaction medium is left at 100° C. After 1.3 and7 hours, 0.75 ml of diphenylphosphine is added. The solution is stirredfor 2 days. It is then cooled to 0° C. and then filtered under argon andwashed with methanol (2×10 ml). Finally, the solid is dried under vacuumto give the expected product in a yield of 50%.

[0485] Elemental analysis for C₄₆H₃₀N₂P₂ calculated: C=80.88; H=4.43;N=4.10; P=9.07; found: C=81.61; H=4.45; N=4.11; P=8.99.

[0486]¹H NMR (CDCl₃, 200 MHz) δ (ppm): 6.59 (d, 2H, CH); 6.87 (dd, 2H,CH); 6.92-6.99 (m, 4H, CH); 7.09 (t, 4H, CH); 7.17-7.31 (m, 12H, CH);7.57 (d, 2H, CH); 7.95 (d, 2H, CH); 8.20 (s, 2H, CH).

[0487]¹³NMR (CDCl₃, 50 MHz) δ (ppm): 109.8 (CH); 119.0 (Cq); 126.3 (CH);127.7 (CH); 128.4 (CH); 128.5 (CH); 128.5 (CH); 128.6 (CH); 128.8 (CH);129.3 (CH); 132.0 (CH); 132.1 (Cq); 132.9 (CH(triplet J_(C-P)=11.7);133.9 (Cq); 134.1 (Cq); 134.9 (CH(triplet J_(C-P)=9.9)); 136.8 (Cq);140.6 (Cq).

[0488]³¹P NMR (CDCl₃81 MHz) δ (ppm): −12.75.

EXAMPLE 2 Preparation of(S)-6,6′-bis(aminomethyl)-2,2′-bis(di-phenylphosphino)-1,1′-binaphthyl(VII: Ar₁=Ar₂=C₆H₅)

[0489] 557 mg (14.7 mmol) of LiAlH₄ are dissolved in a mixture of THF(30 ml)/toluene (60 ml) in a 250 ml round-bottomed flask placed under anargon atmosphere.(S)-6,6′-Dicyano-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (650 mg,0.97 mmol) is added to this solution, which is stirred and refluxed for4 hours. It is then cooled to 0° C. 600 μl of water and 600 μl of 15%NaOH are added. 2 g of Celite are then added and the mixture is filteredthrough a Millipore filter under argon. 60 ml of dichloromethane areadded and the mixture is stirred and filtered again. This operation iscarried out three times. The organic phase obtained is washed withsaturated aqueous NaCl solution and then dried over Na₂SO₄. The solventis evaporated to give a yellow solid (657 mg, quantitative yield)characterized by NMR (proton, carbon and phosphorus) corresponding tothe expected structure.

[0490] Elemental analysis for C₄₆H₃₈N₂P2 calculated: C=80.59; H=6.00;N=3.55; P=7.84; found: C=81.14; H=5.51; N=3.13; P=7.90.

[0491]¹H NMR (CDCl₃, 200 MHz) δ (ppm): 1.68 (s, 4H, NH₂); 3.81 (s, 4H,CH₂); 6.72 (s, 4H, CH); 6.9-7.3 (m, 20H, CH); 7.33 (d, 2H, CH); 7.64 (s,2H, CH); 7.76 (d, 2H, CH).

[0492]³¹P NMR (CDCl₃, 81 MHz) δ (ppm): −15.08.

EXAMPLE 3 Preparation of a Ruthenium Catalyst

[0493] The catalyst is prepared in situ. All the solvents used wererigorously degased and are anhydrous. The reaction medium is maintainedunder an argon atmosphere. The ligand and the metallic precatalyst,bis(2-methyl-allyl) cycloocta-1,5-dieneruthenium, in a ligand/metalmolar ratio of 1:1, are directly weighed out in a 5 ml conical-basedglass reactor taken from the oven and equipped with a stirrer. Thereactor is sealed with a septum and the air is flushed out with an argoninlet. Acetone (1 ml) is then added to give a white suspension. Thissuspension is stirred for 30 minutes and a 0.29 M methanolic HBrsolution is then added (Ru/Br ratio of 1/2.3). A change in the color ofthe solution, which turns brown, is then observed. This solution isstirred for a further 1 hour and the solvent is then evaporated off. Thecatalyst is thus obtained with the appearance of a brown solid.

[0494] Two complexes are prepared according to this procedure.

[0495] The first, Dicyano-BINAP, starting with(S)-6,6′-dicyano-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (obtainedin Example 1).

[0496] The second, Diam-BINAP, starting with(S)-6,6′-diaminomethyl-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl(obtained in Example 2).

EXAMPLE 4

[0497] This example illustrates the hydrogenation of a β-keto ester inthe presence of the ruthenium complexes prepared in Example 3.

[0498] The hydrogenation protocol is described below:

[0499] Methanol which has been predried over magnesium is added (2.5 ml)under argon to the conical reactor in which the catalyst has just beenprepared. The substrate is then added (in a given catalyst/substrateratio). The operation consisting in placing under vacuum and filling thereactor with argon is repeated three times. The septum is then replacedwith a pierced stopper and the reactor is then placed in an autoclave.The autoclave is purged three times with argon and then three times withhydrogen, after which 40 bar of hydrogen pressure is applied. Theautoclave is placed on a hot plate (50° C.) and stirring is maintainedovernight. The conical reactor is finally recovered, the stopper isreplaced with a septum and argon is reinjected into this reactor. Thereactor is placed in a centrifuge and the solution is then extractedusing a syringe. It is placed in a 50 ml round-bottomed flask anddiluted with 20 ml of methanol, thus ready to be injected onto achromatography column for gas chromatography to analyze the degree ofconversion and the enatioselectivity of the reaction.

[0500] More specifically, the determination of the enantiomeric excessesis carried out by chiral gas chromatography on a column ofMacherey-Nagel type (Lipodex A 25 m×0.25 mm).

[0501] The test substrate is a β-keto ester, namely methyl acetoacetate.It gives, after hydrogenation, methyl 3-hydroxybutanoate. The compoundobtained is the S enantiomer, the catalysts being prepared from thecompounds of Examples 1 and 2.

[0502] The results obtained for each of the complexes described inExample 3 above are given in Table 1 below: TABLE 1 Degree ofEnantiomeric Substrate Complex conversion (%) excess (%) MethylDicyano-BINAP 25 100 acetoacetate Methyl Diam-BINAP 100 100 acetoacetate

[0503] By way of comparison, the hydrogenation of methyl acetoacetate iscarried out in the presence of a ruthenium complex prepared from(R)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl. The reaction conditionsfor the hydrogenation and for the preparation of the metal catalyst areas described above. The results obtained are collated in Table 2, itbeing understood that the hydrogenation product is, in this case, methyl(R)-3-hydroxybutanoate. TABLE 2 (comparative) Degree of EnantiomericSubstrate Complex conversion (%) excess (%) Methyl BINAP 100 99acetoacetate

[0504] As may be seen, the complexes prepared from the compounds ofExamples 1 and 2 above give excellent enantiomeric excesses.. Thecatalysts of the invention thus allow a highly enantioselectivehydrogenation reaction to be carried out.

EXAMPLE 5

[0505] This example illustrates the hydrogenation of an aromatic ketonein the presence of the ruthenium complexes prepared in Example 3.

[0506] The hydrogenation protocol followed is as described in Example 4,except that the substrate used is acetophenone. It leads tophenylethanol.

[0507] The determination of the enantiomeric excesses is performed underthe same conditions as in Example 4.

[0508] The results obtained are given in Table 3 below. TABLE 3 Degreeof Enantiomeric Complex conversion (%) excess (%) Dicyano-BINAP 22 2Diam-BINAP 72 18

[0509] By way of comparison, this same substrate was hydrogenated in thepresence of the ruthenium complex with2,2′-bis(diphenylphosphino)-1,1′-binaphthyl prepared in Example 4.

[0510] The hydrogenation reaction conditions are as described above.

[0511] The results obtained are a degree of conversion of less than 1%(traces) and an enantiomeric excess of 0%.

[0512] This example shows very clearly the superiority of the catalystsof the invention.

1. A process for preparing a compound of formula I:

in which: A represents phenyl or naphthyl; and Ar₁ and Ar₂ independentlyrepresent a saturated aromatic or carbocyclic group; this processcomprising the steps consisting in: i) brominating a diol of formula II:

in which A is as defined above, using a suitable brominating agent so asto obtain a dibromo compound of formula III:

in which A is as defined above; ii) esterifying the compound of formulaIII obtained in the preceding step by the action of a sulfonic acid oran activated form thereof, so as to obtain the correspondingdisulfonate; iii) substituting the two bromine atoms with cyano groupsby reacting the disulfonate obtained in the preceding step with asuitable nucleophilic agent so as to obtain the corresponding nitrile;iv) coupling a phosphine of formula VI: XPAr₁Ar₂   VI in which Xrepresents a hydrogen atom or a halogen atom and Ar₁ and Ar₂ are asdefined above, with the nitrile obtained in the preceding step, in thepresence of a catalyst based on a transition metal, so as to obtain theexpected compound of formula I.
 2. The process as claimed in claim 1,characterized in that: A represents naphthyl or phenyl, optionallysubstituted with one or more radicals chosen from (C₁-C₆)alkyl and(C₁-C₆)alkoxy; and Ar₁ and Ar₂ independently represent a phenyl groupoptionally substituted with one or more (C₁-C₆)alkyl or (C₁-C₆)alkoxy;or a (C₄-C₈)cycloalkyl group optionally substituted with one or more(C₁-C₆)alkyl groups.
 3. The process as claimed in either of claims 1 and2, characterized in that Ar₁ and Ar₂ are independently chosen fromphenyl optionally substituted with methyl or tert-butyl; and(C₅-C₆)-cycloalkly optionally substituted with methyl or tert-butyl. 4.The process as claimed in either of claims 1 and 2, characterized inthat Ar₁ and Ar₂ are identical and preferably represent optionallysubstituted phenyl.
 5. The process as claimed in any one of thepreceding claims, characterized in that A represents naphthyl.
 6. Theprocess as claimed in any one of the preceding claims, for thepreparation of an optically active compound of formula I from anoptically active diol of formula II.
 7. The process as claimed in anyone of the preceding claims, characterized in that the bromination isperformed, in step (i) by the action of bromine, at a temperature ofbetween −78° C. and −30° C.
 8. The process as claimed in any one of thepreceding claims, characterized in that, in step (ii), theesterification is carried out by the action of trifluoromethanesulfonicanhydride in the presence of a base, the base preferably being chosenfrom pyridine and 4-dimethylaminopyridine.
 9. The process as claimed inany one of the preceding claims, characterized in that the nucleophilicagent used in step (iii) is CuCN.
 10. The process as claimed in any oneof the preceding claims, characterized in that, in step (iv), HPAr₁Ar₂is reacted with the nitrile in the presence of[bis(diphenylphosphino)ethane]nickel-dichloride and triethylenediamineat a temperature of from 50 to 200° C. and preferably from 80 to 130° C.11. The process as claimed in any one of claims 1 to 9, characterized inthat, in step (iv), a compound of formula XPAr₁Ar₂ (in which X is ahalogen atom), is reacted with the nitrile in the presence of[bis(diphenylphosphino)ethane]nickeldichloride and zinc, at atemperature of between 50 and 200° C. and preferably between 80 and 180°C.
 12. The process as claimed in either of claims 10 and 11,characterized in that the molar ratio of compound VI to the nitrile isbetween 2 and
 4. 13. The process as claimed in any one of claims 10 to12, characterized in that the reaction of the compound of formula VIwith the nitrile is carried out in N,N-dimethylformamide as solvent. 14.A process for preparing a compound of formula VII:

in which A, Ar₁and Ar₂ are as defined in claim 1 or in claim 2,characterized in that it comprises the reduction of the nitrilefunctions of the corresponding compound of formula I as defined in claim1 or in claim 2, respectively, by the action of a suitable reducingagent.
 15. The process as claimed in claim 14, characterized in that thereducing agent is lithium aluminum hydride, the reduction being carriedout in a mixture of toluene and tetrahydrofuran as solvent.
 16. Theprocess as claimed in any one of claims 1 to 13, also comprising thestep consisting in treating the compound of formula I in a basic mediumor in an acidic medium so as to obtain the corresponding carboxylic acidof formula:

in which A, Ar₁ and Ar₂ are as defined in claim 1 or claim
 2. 17. Acompound of formula VII:

in which A, Ar₁ and Ar₂ are as defined in any one of claims 1 to
 5. 18.Use of a compound of formula I obtained by carrying out the process asclaimed in any one of claims 1 to 13, as a ligand for preparing a metalcomplex which is useful in asymmetric catalysis.
 19. The use of acompound of formula VII as claimed in claim 17, as a ligand forpreparing a metal complex which is useful in asymmetric catalysis. 20.The use as claimed in claim 19, characterized in that said complex isintended to catalyze the asymmetric hydrogenation of ketones.
 21. Theuse as claimed in any one of claims 18 to 20, characterized in that themetal complex is a ruthenium, rhodium or iridium complex.
 22. A compoundof formula IV:

in which A is as defined in any one of claims 1 to 5 and P represents ahydrocarbon-based aliphatic group; an aromatic carbocyclic group; or analiphatic group substituted with an aromatic carbocyclic group.